Chemokine (C‐X‐C) Ligand 12 Facilitates Trafficking of Donor Spermatogonial Stem Cells

Niu, Zhiyv; Goodyear, Shaun; Avarbock, Mary R.; Brinster, Ralph L.

doi:10.1155/2016/5796305

Cited by 18 publications

(15 citation statements)

References 34 publications

(58 reference statements)

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“…Requirement for a CXCL12-induced effect on the germ cell population is the expression of respective receptors on the cell surface of spermatogonia. For CXCR4, relevant studies have demonstrated that spermatogonia isolated via the cell surface receptor THY1, display higher expression levels of CXCR4 compared to testicular somatic cells (Oatley et al 2006, Niu et al 2016. More importantly even, CXCR4 protein was localized to the cell surface of spermatogonia residing along the basement membrane in testicular tissues from 3 and 5 days old as well as adult mice (Payne et al 2010, Chen et al 2015, Niu et al 2016.…”

Section: R214mentioning

confidence: 99%

“…For CXCR4, relevant studies have demonstrated that spermatogonia isolated via the cell surface receptor THY1, display higher expression levels of CXCR4 compared to testicular somatic cells (Oatley et al 2006, Niu et al 2016. More importantly even, CXCR4 protein was localized to the cell surface of spermatogonia residing along the basement membrane in testicular tissues from 3 and 5 days old as well as adult mice (Payne et al 2010, Chen et al 2015, Niu et al 2016. Upon induction of meiosis (days 14 and 21 pp), expression of CXCR4 was also detected in differentiating germ cells as well as in spermatids and even interstitial cells in adult testes.…”

Section: R214mentioning

confidence: 99%

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The C-X-C signalling system in the rodent vs primate testis: impact on germ cell niche interaction

Heckmann¹,

Pock²,

Tröndle³

et al. 2018

Reproduction

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In zebrafish, action of the chemokine Cxcl12 is mediated through its G-protein-coupled seven-transmembrane domain receptor Cxcr4 and the atypical receptor Cxcr7. Employing this animal model, it was revealed that this Cxcl12 signalling system plays a crucial role for directed migration of primordial germ cells (PGC) during early testicular development. Importantly, subsequent studies indicated that this regulatory mechanism is evolutionarily conserved also in mice. What is more, the functional role of the CXCL12 system does not seem to be limited to early phases of testicular development. Data from mouse studies rather demonstrate that CXCL12 and its receptors are also involved in the homing process of gonocytes into their niches at the basal membrane of the seminiferous tubules. Intriguingly, even the spermatogonial stem cells (SSCs) present in the adult mouse testis appear to maintain the ability to migrate towards a CXCL12 gradient as demonstrated by functional migration assays and germ cell transplantation assays. These findings not only indicate a role of the CXCL12 system throughout male germ cell development in mice but also suggest that this system may be evolutionarily conserved. In this review, we take into account the available literature focusing on the localization patterns of the CXCL12 system not only in rodents but also in primates, including the human. Based on these data, we discuss whether the CXCL12 system is also conserved between rodents and primates and discuss the known and potential functional consequences.

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Section: R214mentioning

confidence: 99%

Section: R214mentioning

confidence: 99%

The C-X-C signalling system in the rodent vs primate testis: impact on germ cell niche interaction

Heckmann¹,

Pock²,

Tröndle³

et al. 2018

Reproduction

View full text Add to dashboard Cite

show abstract

“…Therefore, there are two problems in repairing Leydig cell dysfunction with ADSCs: one is how to effectively induce ADSCs to migrate to the sites of Leydig cell dysfunction in the testes so that these cells can be regulated by the testicular microenvironment, and the other is how to improve the ability of ADSCs to differentiate into Leydig‐like cells after colonization of the testes. Zhiyv et al reported that the stromal cell‐derived factor‐1 (SDF‐1)/CXC chemokine receptor‐4 (CXCR4) pathway is the most important biological axis for promoting MSC homing to injured tissues and that MSCs positive for CXCR4 expression can migrate to injured tissues with the help of SDF‐1. However, in vitro MSC culture reduces CXCR4 expression and weakens this homing ability.…”

Section: Introductionmentioning

confidence: 99%

CXCR4‐SF1 bifunctional adipose‐derived stem cells benefit for the treatment of Leydig cell dysfunction‐related diseases

et al. 2020

J Cellular Molecular Medi

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Stem cell transplantation is a candidate method for the treatment of Leydig cell dysfunction‐related diseases. However, there are still many problems that limit its clinical application. Here, we report the establishment of CXCR4‐SF1 bifunctional adipose‐derived stem cells (CXCR4‐SF1‐ADSCs) and their reparative effect on Leydig cell dysfunction. CD29+ CD44+ CD34− CD45− ADSCs were isolated from adipose tissue and purified by fluorescence‐activated cell sorting (FACS). Infection with lentiviruses carrying the CXCR4 and SF1 genes was applied to construct CXCR4‐SF1‐ADSCs. The CXCR4‐SF1‐ADSCs exhibited enhanced migration and had the ability to differentiate into Leydig‐like cells in vitro. Furthermore, the bifunctional ADSCs were injected into BPA‐mediated Leydig cell damage model mice via the tail vein. We found that the CXCR4‐SF1‐ADSCs were capable of homing to the injured testes, differentiating into Leydig‐like cells and repairing the deficiency in reproductive function caused by Leydig cell dysfunction. Moreover, we investigated the mechanism underlying SF1‐mediated differentiation and testosterone synthesis in Leydig cells, and the B‐box and SPRY Domain Containing Protein (BSPRY) gene was proposed to be involved in this process. This study provides insight into the treatment of Leydig cell dysfunction‐related diseases.

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“…Hence, in this respect, TPCs significantly complement the roles of Sertoli cells in the formation of a functional spermatogonial stem cell niche. In addition, HTPCs secrete a plethora of factors including the chemokine C‐X‐C motif chemokine ligand 12 (CXCL12) (Flenkenthaler et al ., ), which also plays roles in the regulation of the SSC niche (Westernstroer et al ., ; Niu et al ., ), but is not well examined in the human testis (McIver et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Insights into the role of androgen receptor in human testicular peritubular cells

et al. 2018

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Contractile smooth muscle-like peritubular cells build the wall of seminiferous tubules in men. They are crucial for sperm transport and complement the functions of Sertoli cells by secreting factors, including glial cell line-derived neurotrophic factor. Previous studies revealed that they also secrete the chemokine C-X-C motif chemokine ligand 12 (CXCL12), which has known roles in spermatogenesis. Peritubular cells express the androgen receptor (AR), which is retained in isolated human testicular peritubular cells. We aimed to explore AR-regulated functions in human testicular peritubular cells. Bearing in mind that infertile men often have high aromatase activity, which may lower intratesticular androgen concentrations, an animal model for male infertility was studied. These mice display an age-dependent loss in spermatogenesis due to high aromatase activity. Human testicular peritubular cells were exposed to dihydrotestosterone or the antiandrogen flutamide. We studied AR, smooth muscle cell markers, glial cell line-derived neurotrophic factor and 15 secreted factors previously identified, including CXCL12. We used qPCR, Western blotting, ELISA or selected reaction monitoring (SRM). In the animal model for male infertility, we employed qPCR and immunohistochemistry. Dihydrotestosterone increased AR and flutamide prevented these actions. The smooth muscle cell markers calponin and smooth muscle actin were likewise increased, while cell size or cellular proliferation was not changed. Dihydrotestosterone did not increase glial cell line-derived neurotrophic factor or CXCL12 secretion but increased levels of serine proteinase inhibitor (SERPIN) E1. The animal model for male infertility with high aromatase activity showed reduced numbers of AR-immunoreactive testicular peritubular cells, suggesting that altered androgen and/or oestrogen levels could influence AR-mediated responses in peritubular cells. Androgens act on human testicular peritubular cells to enhance AR levels, their contractile phenotype and to modulate the secretion of some secreted factors. This study suggests that some aspects of human peritubular cell functions are regulated by androgens.

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Chemokine (C‐X‐C) Ligand 12 Facilitates Trafficking of Donor Spermatogonial Stem Cells

Cited by 18 publications

References 34 publications

The C-X-C signalling system in the rodent vs primate testis: impact on germ cell niche interaction

The C-X-C signalling system in the rodent vs primate testis: impact on germ cell niche interaction

CXCR4‐SF1 bifunctional adipose‐derived stem cells benefit for the treatment of Leydig cell dysfunction‐related diseases

Insights into the role of androgen receptor in human testicular peritubular cells

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